Background: Diabetes mellitus (DM) is a metabolic syndrome and a major cause of global mortality rate and concern to health sector. Exploring therapeutic properties of natural plant has attracted array of interests in managing this challenge. This study, therefore, aimed to explore the antihyperglycemic effects of leaf extracts from Artocarpus heterophyllus (A. heterophyllus) in high sucrose diet-treated Drosophila melanogaster (D. melanogaster). Methods: Flies were divided into two groups of 50 flies (both sexes), i.e., i. Survival tests: with high sucrose diet; aqueous extract of A. heterophyllus (AEAH); ethanolic extract of A. heterophyllus (EEAH); and ii. Treatment groups: with AEAH, EEAH, and 30% sucrose diet. Results: The results showed that there was a significant (P<0.05) increase in mortality rate, glucose and oxidative biomarkers such as H2O2, nitrite with a significant (P<0.05) decrease in locomotion (negative geotaxis), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities, as well as total thiol and GSH levels among the high-sucrose diet-treated group compared to normal flies. However, Treatment with AEAH and EEAH resulted in a significant reduction (P<0.05) in mortality rates, glucose levels, and oxidative biomarkers. Additionally, there was a notable increase (P<0.05) in locomotion, as well as in the activities of GPx, CAT, and SOD. This was accompanied by a rise in total thiol and GSH levels when compared to normal flies. Conclusion: Extracts of A. heterophyllus caused a reduction in mortality and enhanced locomotion in D. melanogaster possibly by amelioration of antioxidant imbalance and hyperglycemia.